DESCRIPTION: The proposed work will improve a method for maintaining a steady-state breath alcohol concentration (BAC) while a variety of dependent measures of brain function are assessed. Recovery towards baseline values during the steady state assesses acute tolerance to alcohol, and this study will establish the feasibility of future studies. In addition, the rate of alcohol administration in the clamped and equilibrated steady-state yields a direct measure of the alcohol elimination rate (AER). Health is directly affected by both acute tolerance and the AER because both may be genetically determined and differences among individuals may reinforce or discourage future drinking. In pre studies, adjustments to the rate of an intravenous (iv) infusion of 6% v/v ethanol maintained BrAC within 5 mg% of a 50 mg% target BrAC for prescribed intervals, beginning 42 minutes after an oral loading dose of alcohol in ten male subjects. Event-related potential (ERP) amplitudes provided significant and reliable indices of acute tolerance to alcohol. Three items from the Subjective High Assessment Scale showed significant acute tolerance in subjective perceptions. Retesting AER with the clamp in the ten subjects yielded high reliability, reflected in a coefficient of variation of less than 7%. Accelerating the induction phase of the clamping method should provide increased sensitivity to early phases of the brain's adaptation to alcohol. Thus, the first specific aim is to develop rapid intravenous infusion as a method for achieving a 25 minute start time for the BrAC clamp. The second specific aim is to conduct a pilot study of the sensitivity of acute tolerance indices in subjective, behavioral, and neuropsychological measures, and in a single ERP at two target BrAC. Third, the data will define the sample size of future studies assessing acute tolerance to alcohol in subjects at high risk for alcoholism. Two small studies are proposed. In Study #1, one sample (N=10) is employed once to optimize the new iv induction method; another sample (N=10) is tested twice at 60 mg% to compare the iv induction method to the existing method using oral loading. In Study #2, separate sessions are conducted at target BrACs of 40 and 80 mg% for each of 20 additional subjects, with a third session using an infusion containing no alcohol as a control. Once before and twice during every clamping session of both studies, the battery of dependent measures of brain function are obtained with results reduced to scalar indices, and examined for sensitivity to the effect of alcohol and acute tolerance to alcohol, using the control session to account for learning and fatigue. The indices and the AER will be tested for a preliminary estimate of their dose dependency. Results of this study should provide a firm foundation for application of the clamping technique and dependent measures to important questions in the etiology, genetics and brain function associated with acute tolerance to alcohol.